Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus inturnus (GPi) represent established therapies for medically refractory Parkinson's disease (PD). However, selection of therapeutic stimulation parameters is primarily based on clinical intuition, and the DBS electrode design is not optimized to either nucleus. The fundamental goal of this Bioengineering Research Grant (PA-06-419) is to quantify the volume of tissue activated (VTA) by DBS in PD patients. We recently developed the computational infrastructure necessary to accurately predict the DBS VTA on a patient-specific basis (R21 NS-50449 PI: Mclntyre). In the first aim of the study we will create a patient-specific model of DBS for each subject enrolled in an NIH sponsored clinical trial comparing the therapeutic efficacy of STN DBS to GPi DBS (R01 NS-37959 PI: Vitek). Our central hypothesis is that there exists a target volume of tissue that should be stimulated for maximal therapeutic benefit from DBS, and the size and shape of the target VTA is specific to each nucleus. Characterization of the different anatomical structures activated by DBS across a large patient population (60 STN and 60 GPi) will allow us to define probabilistic maps of therapeutic and non-therapeutic regions for stimulation. These results will allow definition of the therapeutic target VTA for each nucleus. In the second aim of this study we will use our quantitative knowledge of the target VTA for STN DBS and the target VTA for GPi DBS to develop computer algorithms that optimize the clinical selection of therapeutic stimulation parameter settings. We will then prospectively test our patient-specific theoretically optimal stimulation parameter settings on a cohort of 20 new patients. Finally, the third aim of this study will be to design DBS electrodes that are customized to the STN and GPi. We will reverse engineer the design of the DBS electrode such that they generate a VTA shape that better matches the anatomical and electrical constraints of either the target VTA for STN or target VTA for GPi. The scientific knowledge gained from this project will advance the clinical utility of DBS for PD. In addition, the methodology and technology developed in this study will be directly applicable to the study of DBS in other disorders such as essential tremor, dystonia, epilepsy, obsessive-compulsive disorder, depression, and Tourette's syndrome.